tbuckley/cabot-search huggingface dataset:
A phase III double blinded study of early intervention after radical prostatectomy with androgen deprivation therapy with darolutamide versus placebo in men at highest risk of prostate cancer metastasis by genomic stratification (ERADICATE).
Authors: Alicia K. Morgans, Yu-Hui Chen, Anna C. C. Ferrari, Phuoc T. Tran, Edward M. Schaeffer, Daniel H. Shevrin, Russell Zelig Szmulewitz, Thomas Boike, Tanya B. Dorff, Glenn Liu, Lynne I. Wagner, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2022)

TPS5114 Background: Patients with high-risk scores by Decipher molecular testing after prostatectomy have a 5-year metastasis rate of 28% (Decipher 0.6-0.7) and 38% (Decipher &gt; 0.7), likely due to micrometastatic disease. Clinical trials with intensified systemic treatment are warranted to increase cure rates and address this unmet need. Previous studies of adjuvant androgen deprivation therapy (ADT) in clinically identified high-risk disease have not demonstrated substantial benefit other than in men with lymph node positive disease. Darolutamide is a novel androgen receptor antagonist with demonstrated efficacy in improving metastasis-free survival (MFS) and overall survival (OS) in patients with non-metastatic castration-resistant prostate cancer, and OS in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Whether treatment with ADT and darolutamide can increase MFS versus ADT plus placebo in the adjuvant setting for men with molecularly identified high-risk prostate cancer is unknown. Methods: Patients with CAPRA-S scores ≥3 and a PSA &lt; 0.2 after radical prostatectomy undergo Decipher testing provided by the trial. Eligible patients with high-risk Decipher scores (&gt; 0.6) will be randomized to treatment with ADT with darolutamide or placebo for 12 months. Patients are stratified by intent to deliver adjuvant radiation and by baseline PSA (undetectable vs detectable but &lt; 0.2 ng/mL). The primary endpoint is MFS defined by novel PET or conventional imaging. With a sample size of 810 patients, the trial has 80% power with one-sided alpha = 0.025 to detect a HR of 0.60 for the experimental arm vs control arm for the primary endpoint. Secondary endpoints include recurrence-free survival, event-free survival, and quality of life (FACT-P, FACT-Cog, and FACIT-Fatigue), overall survival, and other disease-related outcomes. Trial was activated on December 9, 2020, and is currently enrolling patients. Clinical trial information: NCT04484818.
Efficacy and tolerability of a low dose weekly paclitaxel, carboplatin, cetuximab (PCC) regimen for metastatic or unresectable head and neck squamous cell carcinomas.
Authors: Margaret Locke, Nina Kohn, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2022)

e18019 Background: The standard of care for metastatic or unresectable head and neck squamous cell cancers (HNSCCs) is 5-FU and a platinum doublet with cetuximab or pembrolizumab. However, these regimens are cumbersome as they involve hospitalization for continuous 5-FU infusion and carry a high toxicity profile. In addition, many patients are unfit for this regimen due to poor performance status (PS) or comorbidities. An alternative is paclitaxel, carboplatin, and cetuximab (PCC). PCC has been shown to be a promising induction regimen in small, mostly retrospective studies. Also, low dose chemotherapy may improve tolerability. Our study evaluates the tolerability and efficacy of low dose PCC with or without concurrent palliative radiation therapy (RT) in patients with metastatic or unresectable HNSCCs. Methods: This retrospective observational study included 40 patients with metastatic or unresectable HNSCCs at a single academic center who received PCC between August 2017 and January 2022. Included patients were not candidates for standard frontline therapies due to either PS, comorbidities, prior progression on these therapies, plan for RT, or patient preference. Chart review was performed to grade adverse events (AEs) according to CTCAE criteria. Progression free survival (PFS), overall survival (OS), and response to treatment were assessed per RECIST 1.1 guidelines. Results: Of the 40 patients, mean age was 69.6 years (SD 15.4), and 82.5% were male. Common primary sites were oral (13, 32.5%), oropharynx (12, 30%), hypopharynx (4, 10%), and sinus (4, 10%). Most patients had Stage IVa disease (16, 40%) followed by IVc (12, 30%) and IVb (6, 15%). The remainder (6, 15%) had stage III or unknown stage. Patients received weekly paclitaxel (30-50 mg/m2), carboplatin (AUC 1.5-2), and cetuximab 400 mg/m2 loading followed by 250 mg/m2 maintenance dose. 8 patients (20%) received concurrent RT. Most were treated with palliative intent (32, 80%) and a few induction intent (8, 20%). Prior to PCC, 11 patients had prior salvage surgery, 19 prior RT, and 18 prior systemic therapy. Baseline ECOG PS was 0-2 in 37 patients (92.5%). The most common AEs were skin rash (27, 67.5%), fatigue (22, 55%), and mucositis (12, 30%). 7 patients (17.5%) experienced a grade 3-4 AE, which were mostly hematologic. 2 of the 8 patients on concurrent RT experienced a grade 3-4 AE. 5 patients (12.5%) stopped PCC treatment due to toxicities. 8 patients (20%) had progression on initial follow up imaging. Median duration of response was 4.3 months. PFS was 7.8 months. Median OS was 19.2 months. Conclusions: Our study supports the use of PCC in metastatic or unresectable HNSCCs. This regimen can be considered in patients with suboptimal PS who are not candidates for standard frontline therapies or for those planned for palliative RT. PCC can be used safely and effectively with or without concurrent RT.
Treatment with anti-spike monoclonal antibodies in allogeneic HCT and CAR T-cell recipients with mild to moderate COVID-19: The Mayo Clinic experience.
Authors: Razan Mohty, Matthew Thoendel, Samuel Swei, Radhika Bansal, Jeanne Palmer, William J. Hogan, Paschalis Vergidis, Javier Munoz, Madiha Iqbal, Farah Yassine, Nabila Nora Bennani, Matthew Hathcock, Hemant S. Murthy, Januario E. Castro, Yi Lin, Raymund R. Razonable, Mohamed Kharfan-Dabaja
Journal: Journal of Clinical Oncology (2022)

e19049 Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]
Efficacy and safety of low-dose apatinib in advanced hepatocellular carcinoma.
Authors: Lingbin Meng, Zhuangzhuang Zheng, Rui Ji, Xiaochun Xu, Ying Xin, Xin Jiang
Journal: Journal of Clinical Oncology (2022)

4104 Background: Apatinib, a tyrosine kinase inhibitor, has shown promising effects on advanced hepatocellular carcinoma (HCC) recently. However, studies on its efficacy and safety are limited with controversial findings. Therefore, this study aimed to reveal the efficacy and safety of low-dose apatinib for the treatment of advanced HCC in the real world. Methods: Between January 2017 and August 2020, 178 patients with advanced HCC treated with apatinib at three different institutions were included for the present study. 174 patients received oral apatinib 250 mg daily and 4 received 500 mg daily until disease progression. 25 and 103 patients were also treated with immunotherapy and transcatheter arterial chemoembolization (TACE) at least once, respectively. Tumor response and adverse reactions were evaluated according to RECIST 1.1 and CTCAE 5.0 respectively. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of variables in a univariate and multivariate setting. Results: During the 24-month follow-up period, 0 (0%), 28 (15.73%), 103 (57.87%) and 47 (26.40%) patients achieved a compete response (CR), partial response (PR), stable disease (SD), and progressive disease (PR), respectively. The overall response rate (ORR) and disease control rate (DCR) were 15.73% and 73.60% respectively. Interestingly, among the 28 patients with PR, 27 received apatinib as the first or second line treatment and 21 received immunotherapy or TACE as a combined treatment, indicating early application of apatinib and combination treatment could provide better efficacy. Kaplan-Meier analysis revealed the median overall survival (OS) and progressive-free survival (PFS) were 16.0 and 7.0 months respectively, which are significantly higher than previously reported survival of sorafenib in advanced HCC. Univariate Cox analysis indicated medication lines, distant metastasis, aplpha fetoprotein (AFP) level, portal vein tumor thrombus (PVTT) and combination therapy significantly affected OS and PFS. Multivariate Cox analysis confirmed third-line treatment (HR = 3.21; 95%CI = 1.54–6.68; p= 0.002), and PVTT (HR = 1.75; 95%CI = 1.13–2.70; p= 0.011) were independently associated with worse PFS. In contrast, apatinib combined with immunotherapy (HR = 0.52; 95%CI = 0.32–0.83; p= 0.008) or TACE (HR = 0.27; 95%CI = 0.18–0.40; p&lt; 0.001) were independently associated with better PFS. Similar findings were also present on OS. The most common treatment-related adverse events were hypertension (29.21%), fatigue (16.85%), hand and foot syndrome (16.29%), vomiting (14.04%), liver dysfunction (6.18%), and proteinuria (6.74%). No severe (grade ≥3) adverse events were observed. Conclusions: Low-dose apatinib is able to provide effective and safe treatment for advanced HCC. Early application of apatinib and combination treatment could provide even better efficacy.
Death with dignity utilization among patients with thoracic, head, and neck cancer.
Authors: Natalie F. Uy, Cristina P. Rodriguez, Courtney Daum, Kelsey K. Baker, Jonathan Singer, James Hnida, Laura Lavell, Katie Sofie, Jourdan Cruz, Keith D. Eaton, Rafael Santana-Davila, Elizabeth Trice Loggers
Journal: Journal of Clinical Oncology (2022)

12032 Background: Death with Dignity (DWD) legislation, which took effect in 2009 in Washington state, allows terminally ill patients (pts) to self-administer physician-prescribed, life-ending medication. Thoracic, head and neck cancer (THN) pts are among the top cancer types requesting DWD; however, data describing this group are limited. Methods: This retrospective chart review, conducted at Seattle Cancer Care Alliance/University of Washington and Fred Hutch, collected demographics, disease, treatment, support services and steps of the DWD process. We tested the association between disease characteristics of interest and DWD completion using Fisher’s Exact test. Results: Between Jan 2014 and October 2020, 498 pts inquired about DWD, and 108 (22%) were THN pts. Among THN pts, 51 (47%) only initiated the DWD request process, 35 (33%) only completed the DWD request process, and 22 (20%) completed the DWD request and self-administered the medication. Pts were white (n=90, 83%), male (n=64, 59%), primarily English speaking (n=103, 95%), nonreligious (n=69, 64%), single/divorced/non-partnered (n=55, 51%), and insured (n=103, 95%). Median age at request was 68 years (range 35-88). The table details THN DWD utilization. At time of DWD request, the median time from diagnosis was 14 months (range=0.2-242.7), and 62 (57%) had received ≥2 lines of therapy. Among 78 (72%) pts who received systemic therapy, 51 (65%) were ≥30 days from last therapy to time of death. Within 30 days prior to DWD request, 30 (28%), 25 (23%), and 7 (7%) pts saw social work, palliative care, and spiritual health respectively, and 35 (32%) were hospice-enrolled. Stage IV at diagnosis had higher rates of DWD medication use (p=0.05). There was no significant correlation between DWD medication use and primary site, ECOG score at request, insurance type, mental health diagnosis, use of depression/anxiety or pain medications, or hospice enrollment during DWD process. Conclusions: THN pts requesting DWD were predominantly white, nonreligious, insured males. Pts with advanced stage at diagnosis were more likely to use DWD medication. There was a higher proportion of DWD medication use with poorer performance status, and no association between use of depression/anxiety, pain medications, or utilization of supportive care services and DWD medication usage. Future research should investigate DWD utilization among THN pts in multiple centers and states to evaluate these patterns. [Table: see text]
DETECTION phase II/III trial: Circulating tumor DNA–guided therapy for stage IIB/C melanoma after surgical resection.
Authors: Rebecca Lee, Dominic G. Rothwell, Richard Jackson, Nigel Smith, Stephen Q Wong, Noel Kelso, George Burghel, Chelsee Hewitt, Harry Clarke, Jackie Mitchell, Kate Jones, Andrew Muinonen-Martin, Samra Turajlic, Philippa Gail Corrie, Richard Marais, Mark R. Middleton, Sarah-Jane Dawson, Shahneen Sandhu, Caroline Dive, Paul Lorigan
Journal: Journal of Clinical Oncology (2022)

TPS9603 Background: Circulating tumor DNA (ctDNA; the tumor derived fraction of circulating free DNA in the blood) is a well recognized, minimally-invasive biomarker of tumor burden/progression in many cancers. We have previously shown in retrospective and prospective cohorts of patients with melanoma that ctDNA analysis of serial blood samples following curative intent surgery can identify minimal residual disease (MRD) or molecular relapse. The majority of patients with resected stage II melanoma do not recur, therefore better strategies to identify high risk patients are required. Furthermore, a consistent finding in studies of immune therapy in stage IV melanoma is that patients with small volume disease have the best outcome. We aim to test whether early relapse can be identified by ctDNA analysis and acted upon in a clinically relevant timeframe, and if early treatment of molecular recurrence with immune therapy improves outcomes for patients with resected stage IIB/C melanoma. Methods: We designed a phase II/III multicenter study across 21 UK and 4 Australian sites with a tumor informed approach employed for ctDNA detection. Droplet digital assays for BRAF/NRAS/TERT promoter mutations were validated for sensitive ctDNA detection across two accredited clinical testing laboratories. Patients with stage IIB/C melanoma, BRAF/NRAS/TERT promoter mutant cutaneous melanoma, ECOG 0/1, adequate organ function, with complete resection (including sentinel lymph node biopsy) performed within 12 weeks and radiological/clinical disease-free status confirmed within 4 weeks prior to registration, no prior immune/targeted therapy will be followed up with blinded ctDNA sampling in addition to clinical follow-up. Patients with ctDNA detected will be randomised 1:1 in a double blind fashion to continue routine follow-up with investigators choice treatment if they develop disease recurrence, or unblinded and treated with nivolumab 480mg IV Q4-weekly. Primary objectives include i) whether MRD/molecular relapse following curative intent surgery can be identified earlier than clinical relapse, ii) whether early treatment of molecular recurrence with nivolumab improves overall survival. 1050 patients are planned to be enrolled. The study opened in the UK in November 2021 and will open in Australia in Spring 2022. Clinical trial information: NCT04901988.
Impact of hospital teaching status on outcomes of colorectal cancer in hispanic patients: A nationwide analysis.
Authors: Umer Farooq, Diana Franco, Ghulam Ghous, Irene Ma
Journal: Journal of Clinical Oncology (2022)

e15520 Background: Previous studies described lower mortality in teaching hospitals after colorectal surgery. Hispanics represent a growing minority in the USA. Given their scarcity of representation in clinical studies, it is imperative to study the impact of teaching status on hospital outcomes from colorectal cancer (CRC) in the Hispanic population. Methods: We investigated the National Inpatient Sample 2017-2019 using International Classification of Diseases-10 (ICD-10) codes to include adult Hispanics with CRC. Mortality, morbidity, resource utilization, and surgical outcomes were compared stratified by hospital teaching status. Analyses were performed using STATA (v 14.2), considering 2 sided P&lt; 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student's t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: Out of 72,599 included patients, 15,895 were treated at non-teaching and 56,704 at teaching hospitals. Patients treated at teaching hospitals had 21% lower odds of inpatient mortality (Adjusted odds ratio (aOR) for mortality 0.79, 95% confidence interval (CI): 0.64 – 0.97, P= 0.03). There were no differences between markers of resource utilization (length of stay, hospital charges, and ICU admission). Patients at teaching hospitals had higher odds of acute renal failure (aOR 1.15, 95% CI: 1.02 – 1.30, P= 0.02). Rates of acute respiratory failure, lower GI bleeding, and sepsis were comparable between the two groups. Colectomy and procedure-related complication rates (including intubation, post-operative DVT/PE) were equal between the two studied groups except for post-operative adhesions, which were higher at teaching hospitals (aOR 1.29, 95% CI: 1.05 – 1.58, P= 0.01). Conclusions: There appears to be no difference in colectomy rates in teaching or non-teaching hospitals, which results in comparable in-hospital mortality in Hispanics. However, ARF and post-operative adhesions were more in teaching hospitals. Continued efforts are required to provide better access to healthcare and address morbidity disparities while caring for minorities.[Table: see text]
Impact of <i>EGFR<sup>A289T/V</sup></i>mutation on relapse pattern in glioblastoma.
Authors: Fontanilles Maxime, Alexandra Noeuveglise, Nasrin Vasseur, Ludivine Beaussire, Florent Marguet, Romain Modzelewski, Chantal Hanzen, Cristina Alexandru, Nicolas Magne, Olivier Langlois, Frédéric Di Fiore, Florian Clatot, Sébastien Thureau
Journal: Journal of Clinical Oncology (2022)

2046 Background: The prediction of the relapse pattern is an important issue in glioblastoma for personalized approach. Molecular factors, such as MGMT promoter methylation, influence relapse in- or out-field of the initial radiotherapy volume. Recently, a recurrent mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor ( EGFR A289mut ) has been associated with a more infiltrative phenotype in glioblastoma. The primary objective of the present study was to explore the impact of EGFR A289mut on the pattern of relapse after a chemo-radiotherapy based treatment of patients suffering from glioblastoma. Methods: An ancillary study from a monocentric prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFR A289 status (mutated versus wild-type). Primary endpoint was the overlap score (varying from 0 to 1) between initial irradiated tumor volume (Vinit) and relapse volume (Vr). Vinit was the initial 95% isodose of the radiotherapy and Vr was delineated using the enhanced MRI T1-weighted part of the relapse tumor. Secondary endpoints explored the impact of other EGFR extracellular mutations, EGFR amplification and EGFRvIII on the relapse pattern, as well as the impact of EGFR A289mut on survival. EGFR alterations were identified using next-generation sequencing or droplet-digital PCR based methods on formalin-fixed paraffin-embedded samples collected at initial diagnosis. Results: One hundred patients were included: 11% of the population had EGFR A289mut glioblastoma (n = 11/100). EGFR A289mut glioblastomas had a relapse pattern more marginal compared to EGFR A289wt glioblastomas: a mean overlap score Vinit/Vr of 0.78 was observed in the EGFR A289mut group versus 0.94 in the EGFR A289wt group (p = 0.021). The proportion of EGFR A289mut glioblastomas in the outfield relapse (overlap score &lt; 0.8) has a trend to be higher than in the infield relapse (overlap score &gt; 0.8): 25% (n = 2/8) versus 9.8% (n = 9/92) for the EGFR A289wt population, p = 0.21. Neither EGFR amplification nor EGFRvIII did influence overlap score Vinit/Vr. In our population, EGFR A289mut did not influence survival. Conclusions: EGFR A289mut influences the relapse pattern in a population of patients suffering from glioblastoma. The role of EGFR A289mut as a decision-making biomarker for personalized radiotherapy should now be investigated in dedicated clinical trial. Clinical trial information: NCT02617745.